2020
Assessing Effects of BHV-0223 40 mg Zydis Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym
Longo D, Shoda L, Howell B, Coric V, Berman R, Qureshi I. Assessing Effects of BHV-0223 40 mg Zydis Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym. Toxicological Sciences 2020, 175: 292-300. PMID: 32040174, PMCID: PMC7253195, DOI: 10.1093/toxsci/kfaa019.Peer-Reviewed Original ResearchConceptsOral tabletsALT elevationLiver toxicityClinical dataFirst-pass liver metabolismLiver function test parametersFirst-pass hepatic metabolismLiver toxicity riskAlanine transaminase levelsRelative risk reductionLower overall doseAmyotrophic lateral sclerosisALT levelsTransaminase levelsLiver exposureSublingual formulationHepatic metabolismLateral sclerosisRiluzoleLiver metabolismULNInterindividual variabilityOverall doseHepatotoxicity potentialOxidative stress
2015
Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial
Coric V, Salloway S, van Dyck CH, Dubois B, Andreasen N, Brody M, Curtis C, Soininen H, Thein S, Shiovitz T, Pilcher G, Ferris S, Colby S, Kerselaers W, Dockens R, Soares H, Kaplita S, Luo F, Pachai C, Bracoud L, Mintun M, Grill JD, Marek K, Seibyl J, Cedarbaum JM, Albright C, Feldman HH, Berman RM. Targeting Prodromal Alzheimer Disease With Avagacestat: A Randomized Clinical Trial. JAMA Neurology 2015, 72: 1324-1333. PMID: 26414022, DOI: 10.1001/jamaneurol.2015.0607.Peer-Reviewed Original ResearchConceptsNonmelanoma skin cancerObservational cohortProdromal Alzheimer's diseaseProdromal ADClinical trialsPositron emission tomographyAlzheimer's diseaseDiscontinuation ratesCSF biomarkersBiomarker criteriaTreatment phasePlacebo-controlled phase 2 clinical trialSkin cancerGastrointestinal tract adverse eventsKey clinical outcome measuresSerious adverse event ratesΓ-Secretase Inhibitor AvagacestatEmission tomographyPhase 2 clinical trialPotential disease-modifying agentsBrain atrophy ratesLow discontinuation rateAdverse event ratesDisease-modifying agentsGreater brain atrophy
2012
Safety and Tolerability of the γ-Secretase Inhibitor Avagacestat in a Phase 2 Study of Mild to Moderate Alzheimer Disease
Coric V, van Dyck CH, Salloway S, Andreasen N, Brody M, Richter RW, Soininen H, Thein S, Shiovitz T, Pilcher G, Colby S, Rollin L, Dockens R, Pachai C, Portelius E, Andreasson U, Blennow K, Soares H, Albright C, Feldman HH, Berman RM. Safety and Tolerability of the γ-Secretase Inhibitor Avagacestat in a Phase 2 Study of Mild to Moderate Alzheimer Disease. JAMA Neurology 2012, 69: 1430-1440. PMID: 22892585, DOI: 10.1001/archneurol.2012.2194.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesBody WeightDose-Response Relationship, DrugDouble-Blind MethodEnzyme InhibitorsFemaleHumansImmunoprecipitationInternational CooperationMagnetic Resonance ImagingMaleMass SpectrometryMiddle AgedNeuropsychological TestsOutcome Assessment, Health CareOxadiazolesPsychiatric Status Rating ScalesSulfonamidesTau ProteinsTime FactorsConceptsPhase 2 studyModerate Alzheimer's diseaseAdverse eventsAlzheimer's diseaseDiscontinuation ratesDose groupPharmacodynamic effectsAlzheimer's Disease Assessment Scale-cognitive subscale scoresTreatment-emergent serious adverse eventsDouble-blind treatment phaseΓ-Secretase Inhibitor AvagacestatSerious adverse eventsLow discontinuation rateNonmelanoma skin cancerCognitive subscale scoresDose armBiomarker substudyMedian ageMulticenter trialAcceptable safetyCognitive worseningΕ4 carriersCommon reasonTreatment groupsTreatment phase
2010
Multicenter, randomized, double‐blind, active comparator and placebo‐controlled trial of a corticotropin‐releasing factor receptor‐1 antagonist in generalized anxiety disorder
Coric V, Feldman HH, Oren DA, Shekhar A, Pultz J, Dockens RC, Wu X, Gentile KA, Huang S, Emison E, Delmonte T, D'Souza BB, Zimbroff DL, Grebb JA, Goddard AW, Stock EG. Multicenter, randomized, double‐blind, active comparator and placebo‐controlled trial of a corticotropin‐releasing factor receptor‐1 antagonist in generalized anxiety disorder. Depression And Anxiety 2010, 27: 417-425. PMID: 20455246, DOI: 10.1002/da.20695.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnti-Anxiety AgentsAnxiety DisordersCitalopramDiagnostic and Statistical Manual of Mental DisordersDouble-Blind MethodFemaleHumansMaleMiddle AgedPharmacogeneticsPhenotypePolymorphism, Single NucleotidePsychometricsPyrazolesReceptors, Corticotropin-Releasing HormoneSeverity of Illness IndexTriazinesYoung AdultConceptsGeneralized anxiety disorderSingle nucleotide polymorphismsHamilton Anxiety Scale (HAMA) total scoreAnxiety disordersFactor receptor 1 antagonistActive comparator armCorticotropin-releasing factor receptorsActive comparator trialsPlacebo-controlled trialCorticotropin-releasing factor receptor 1 antagonistTreatment of GADPrimary outcome measurePlexin-A2Receptor 1 antagonistScale total scoreCRF-1 receptor antagonistClass of agentsComparator trialsComparator armPrimary outcomeActive comparatorEntire cohortRandomized subjectsReceptor antagonistMean change